Standard surgical procedures require disinfection of skin surfaces of the surgeon, the operating staff, and patient at the surgical site prior to surgery. Effective pre-operative cleansing of skin is critical to reducing the risk of infection to the patient. Surgical scrub and pre-operative skin preparations are therefore important to control the risk of infection.
Microorganisms on the skin can be transient or resident. Transient microorganisms are introduced onto the skin via the environment and lie on the surface of the skin, whereas resident microorganisms are evolved to survive and grow on the skin and are found at the surface as well as at deeper sites in the skin.
Surgical hand antisepsis is an antiseptic handwash or antiseptic hand rub performed preoperatively by surgical personnel to eliminate transient and reduce resident hand flora. This may also be referred to as disinfection. Patient skin antisepsis is also required to disinfect the site of the surgery.
Effective antiseptic compositions can be produced by combining a surfactant or detergent with an antimicrobial agent. However, many such compositions are harsh or unsuitable for contact with human skin, and can cause discomfort and irritation to the skin. The development of formulations containing antimicrobial agents and detergents that provide acceptable antiseptic properties as well as avoid skin irritation has proven difficult, since the effectiveness of the antimicrobial agent is often reduced by the additional ingredients used.
United States Food and Drug Administration (FDA) developed performance standards for new and novel antiseptic compositions. These performance standards require a surgical hand scrub to be broad spectrum, fast acting, and persistent. The term broad spectrum is defined in this instance as having antimicrobial activity against a variety of gram positive and gram negative bacteria, and yeasts. The FDA also set forth testing procedures by which new antiseptics are tested alongside previously approved products. Requirements for patient preoperative skin preparation are outlined in the FDA Tentative Final Monograph for Healthcare Antiseptic Drug Products (TFM) (Federal Register 59 [116], Jun. 17, 1994: pp. 31402-31452).
Requirements for in vitro and in vivo testing of surgical hand scrubs are outlined in the FDA Tentative Final Monograph for Healthcare Antiseptic Drug Products (TFM) (Federal Register 59 [116], Jun. 17, 1994: pp. 31445-31448). The in vivo test procedure described beginning on page 31445 will hereinafter be referred to as the FDA TFM surgical hand scrub test.
The antimicrobial efficacy of Surgical Scrubs can also be tested by any appropriate recognized test to demonstrate adequate disinfection of resident skin flora. Examples of such tests are ASTM E 1115-02, “Standard Test Method for Evaluation of Surgical Hand Scrub Formulations” (ASTM International) and EN 12791:2005, “Chemical disinfectants and antiseptics, Surgical hand disinfection, Test method and requirement (phase 2, step 2),” (CEN-Comitée Européen de Normalisation, Brussels, Belgium). ASTM E 1173-01 provides “Standard Test Method for Evaluation of Preoperative, Precatheterization, or Preinjection Skin Preparations.”
The product to be tested according to the FDA TFM surgical hand scrub test is used eleven times over a period of five days, and the reduction of resident skin flora is measured after the first wash on days 1, 2, and 5. Measurements are also done 3 and 6 hours after these washes, to measure persistence. The FDA TFM surgical hand scrub test requires that formulations reduce the number of bacteria 1 log10 on each hand within 1 minute of product application and that the bacterial cell count on each hand does not subsequently exceed baseline within 6 hours on day 1; the formulation must produce a 2 log10 reduction in microbial flora on each hand within 1 minute of product application by the end of the second day of enumeration and a 3 log10 reduction of microbial flora on each hand within 1 minute of product use by the end of the fifth day when compared with the established baseline.
Numerous attempts have been made to develop formulations that provide effective antiseptic or disinfectant properties and that meet the requirements of the glove juice test. However, the efficacy of antiseptic or disinfectant compositions is greatly influenced by a number of variables, including concentration of organisms, duration of exposure, concentration of the antiseptic and the type of surfactants used in the formulation.
Formulations containing the antimicrobial agent chlorhexidine have been used as antibacterial skin cleaners in surgical scrubs. For example, Billany et al., U.S. Pat. No. 3,960,745, discloses a chlorhexidine cleansing composition formulated with a polyoxyethylene-polyoxypropylene nonionic surfactant.
Other formulations have used bisbiguanide as an antimicrobial agent as disclosed in U.S. Pat. No. 4,456,543 to Ownes. The '543 patent discloses an antibacterial cleansing formulation containing bisbiguanide and one or more nonionic polyoxyalkylene surfactants.
Dewar et al., U.S. Pat. No. 4,157,977 discloses surfactant-germicide compositions containing an antimicrobial active phenolic derivative in combination with hydroxyacetic acid and a surfactant.
Casey et al., U.S. Pat. No. 4,252,665 and Langguth et al., U.S. Pat. No. 4,257,907 disclose a disinfectant cleaning composition containing ortho-benyzl-para-chlorophenol, anionic surfactants and sulfobetaine surfactants.
Meldovanyl et al., United Kingdom Application 2 203 339, discloses an aqueous microbicidal formulation containing (A) a microbicidal active substance such as benzalkonium chloride, (B) a dispersing active substance such as certain carboxylic acids, and (C) a solubilizing agent such as propylene glycol.
Formulations containing the antimicrobial agent parachlorometaxylenol (PCMX) have been disclosed in a number of patents. U.S. Pat. No. 4,632,772 to Garabedian et al. discloses an antimicrobial composition containing the active antimicrobial agent PCMX and an ionic surfactant, alkyl aryl ethoxylated sulfonate. Melvin, U.S. Pat. No. 3,326,808 discloses an antiseptic surfactant composition containing PCMX and an anionic surfactant, the sodium salt of 2-sulfomethyl myristate. U.S. Pat. No. 6,413,921 teaches a composition that can be used as a surgical scrub formulation or pre-surgical skin disinfecting formulation. The pre-operative antimicrobial skin composition comprises parachlorometaxylenol (PCMX) as the antimicrobial agent and an anionic surfactant composition comprising a surfactant having a hydrophobic portion consisting of a linear alkyl and a hydrophilic portion having ethoxylation termination with a sulfonate anionic group; and a sarcosine surfactant.
Because of the rapid bactericidal activity of lower alcohols, numerous inventions have centered around alcohol-containing surgical scrub technologies. White, European Patent Application 0 223 681, discloses an alcohol-based antimicrobial composition that includes a viscosifying agent such as hydroxypropyl cellulose.
U.S. Pat. No. 6,110,908 to Guthery teaches an antiseptic composition claiming broad spectrum, fast acting and persistent effect, that includes 70% antibacterial alcohol, an antimicrobial lipid such as free fatty acids and/or fatty acid esters, and zinc pyrithione or zinc omadine. However, free fatty acids can be skin irritants. Also, compositions containing zinc pyrithione or zinc omadine are generally solid suspensions, and separation can occur over time, shortening shelf-life of the product.
U.S. Pat. No. 6,090,395 teaches a viscous pre-surgical scrub containing a lower alcohol and water in a weight ratio of about 35:65 to about 100:0, which is thickened to a viscosity of at least 4,000 centipoise, by using an emulsifier system. A secondary antimicrobial component such as chlorhexidine gluconate (CHG) may be added to achieve the efficacy required for surgical scrubs. However, it has been found that irritation due to CHG sensitivity can occur.
U.S. Pat. No. 6,723,689 teaches an antimicrobial composition that includes alcohol in an amount from about 60 to about 95 weight percent, a preservative, a cationic cellulose polymer thickening agent, a moisturizer and/or a cationic emulsifier, and water. The antimicrobial composition was tested according to the FDA glove juice test, and exhibited a 3.03 log kill on day 3 of the test (3.47 log kill when 4 percent by weight CHG was added). The compositions reported to pass the FDA requirements for surgical scrubs contain CHG. As stated above, CHG sensitivity can result in irritation to the skin. The '689 patent includes comparative test data showing that formulations according to the '908 patent and the '395 patent did not meet the 3 log kill requirement as of day 3.
U.S. Published Application No. 2004/0247685 A1 teaches a hydroalcoholic antimicrobial composition that includes octoxyglycerin (Sensiva®) and at least one other antimicrobial agent, such as biguanides or phenols. U.S. Published Application No. 2005/0238602 A1 teaches a hydroalcohol gel surgical hand wash comprising: (i) two or more organic salts of zinc; (ii) farnesol; (iii) panthenol; and (iv) a quaternary ammonium compound and a biguanide. In order to maintain antimicrobial efficacy, these components are used in conjunction with various combinations of chlorhexidine gluconate, benzalkonium chloride, incroquat and Sensiva.® There is no suggestion that the compositions of the '602 or '685 published applications have adequate antimicrobial efficacy without these additional antimicrobial agents.
U.S. Pat. No. 6,319,958 describes attempts to increase the efficacy of antimicrobial agents by using sesqueterpenoids. However, studies suggest that sesqueterpenoids can cause irritation to human skin.
Therefore, each of the current pre-surgical disinfecting products has one or more short-comings. These short-comings include irritation to the skin, stickiness, a greasy feel, and inadequate efficacy. A need continues to exist for topical compositions that have rapid efficacy against both transient and resident microorganisms on the skin, very low toxicity, and good aesthetics. More specifically, it would be desirable to have a surgical scrub and pre-operative skin preparation without the above shortcomings that meets the requirements for antiseptics as outlined in the FDA Tentative Final Monograph for Healthcare Antiseptic Drug Products (TFM). Particularly, it would be desirable to have a surgical hand scrub that meets the requirements of the FDA TFM surgical hand scrub test.